Epilepsy is one of the most common neurological disorders, affecting 50 million people worldwide, and in approximately 30% of these patients the seizures are not controlled by any available drug therapy. Partial epilepsy (seizures that begin in a focal region of the brain) represents the most common type of intractable epilepsy, and can be difficult to treat. Epilepsy surgery has the best chance of producing a cure, i.e. complete seizure freedom, but is a viable option only if the brain region generating seizures can be accurately localized and safely removed. Thus, accurate localization of epileptogenic foci responsible for seizures is of paramount importance for successful epilepsy surgery. The goal of the proposed research is to establish, evaluate and validate a novel computational imaging approach (3D-FINE imaging) for high resolution localization and imaging of epileptogenic foci within the 3-dimensional brain from noninvasive scalp EEC recordings and patients' structure imaging such as MRI and CT. Innovative computational methods are proposed including a novel subspace source localization method and an innovative causality analysis algorithm for high resolution seizure foci localization and imaging. Furthermore, we propose to rigorously validate the proposed epileptogenic source imaging methods in 100 adult and pediatric epilepsy patients, by comparing the noninvasive brain source imaging with intracranial recordings, other clinical imaging, and surgical outcome. The specific aims are: 1) Development of 3D-FINE for high-resolution imaging and localization of epileptogenic foci, including rationale determination of order of signal subspace, boundary and finite element modeling, and coherence analysis of source imaging results; 2) Evaluation and optimization of 3D-FINE by systematic computer simulations; 3) Validation of 3D-FINE from intracranial recordings, other clinical imaging results, and surgical outcome in adult patients; and 4) Validation of 3D-FINE from intracranial recordings, other clinical imaging results, and surgical outcome in pediatric patients. The established clinical practice is to use intracranial recordings to aid presurgical planning, which represents significant risks and expenses to the patients and healthcare system. The present application addresses the practical problem of developing noninvasive means of identifying epileptogenic foci which may substantially reduce the need for invasive mapping in patients with intractable epilepsy. The successful completion of the proposed research will substantially advance the state-of-the-art of management of intractable epilepsy and functional brain mapping. The availability of a noninvasive imaging technology to identify and image the epileptogenic foci would benefit numerous patients suffering from epilepsy and the healthcare system. [unreadable] [unreadable] [unreadable]